Groupe de Recherche Clinique Neurométabolique, Université Pierre et Marie Curie, Paris, France.
Centre de Référence Neurométabolique Adulte, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
J Inherit Metab Dis. 2018 Sep;41(5):753-756. doi: 10.1007/s10545-018-0209-9. Epub 2018 Jun 6.
Until recently, inborn errors of metabolism (IEM) were considered a pediatric specialty, as emphasized by the term "inborn," and the concept of adult onset IEM has only very recently reached the adult medical community. Still, an increasing number of adult onset IEM have now been recognized, as new metabolomics and molecular diagnostic techniques have become available. Here, we discuss possible mechanisms underlying phenotypic variability in adult versus children with IEM. Specifically, phenotypic severity and age of onset are expected to be modulated by differences in residual protein activity possibly driven by various genetic factors. Phenotypic variability may also occur in the context of similar protein expression, which suggests the intervention of environmental, ontogenic, and aging factors.
直到最近，先天性代谢缺陷（IEM）仍被认为是儿科的一个专业领域，这一点从术语“先天性”就可以看出，而成人发病 IEM 的概念直到最近才被成人医学领域所接受。尽管如此，随着新的代谢组学和分子诊断技术的出现，越来越多的成人发病 IEM 现在已经被认识到。在这里，我们讨论了成人和儿童 IEM 表型变异性的可能机制。具体而言，表型严重程度和发病年龄预计会受到各种遗传因素驱动的残余蛋白活性差异的调节。表型变异性也可能发生在类似蛋白表达的情况下，这表明环境、个体发生和衰老因素的干预。
